Degeneration of retinal photoreceptor neurons, such as that seen in age-related macular degeneration (AMD), is the most common cause of blindness in the United States. There are compelling reasons to believe that subretinal cell transplantation could be used to replace missing photoreceptor neurons. No effective and practical source of cells for transplantation is currently available. The goal of this project is to develop cells to be used for transplantation to replace photoreceptor neurons in AMD and related diseases. Bone marrow-derived stem cells offer numerous advantages over other cell types as a possible source of donor cells. These cells can differentiate into neurons. They are readily available, and if used for autologous transplantation to the retina, they would not have the same immunological consequences inherent in the use of other cell types. To our knowledge, no other laboratories are investigating bone marrow-derived stem cells for transplantation to the retina. At this time, there is no evidence that bone marrow-derived stem cells can differentiate into retinal neurons. The specific aim of this preliminary investigation is to determine conditions that would allow these cells to differentiate as photoreceptor neurons or other retinal cell types. The study has three sequential steps. First, treat GFP-labeled, bone marrow-derived stem cells in ways likely to induce the photoreceptor phenotype. This includes culturing cells in factors such as FGF-2, EGF, retinoic acid, sonic hedgehog and taurine, and/or transfecting the cells with a gene for the photoreceptor cell specific transcription factor, Crx. Second, co-culture treated bone marrow-derived stem cells with embryonic retina or transplant the cells to the subretinal space in animals depleted of photoreceptor cells. Third, assess histologically the differentiation of bone marrow-derived stem cells in the retinal co-cultures or after transplantation to the retina by determining their laminar distribution in the host retina and by immunohistochemistry with antibodies specific to retinal cell types.